Effects of isoflavones on breast density in pre- and post-menopausal women: a systematic review and meta-analysis of randomized controlled trials. Hum Reprod Update

SRD Senior Lecturer in Research Synthesis and Nutrition, School of Medicine, University of East Anglia, Health Policy and Practice, Norwich NR4 7TJ, Norfolk, UK.
Human Reproduction Update (Impact Factor: 8.66). 10/2010; 16(6):745-60. DOI: 10.1093/humupd/dmq011
Source: PubMed

ABSTRACT Isoflavones from soy and red clover exert modest hormonal effects in women, but the relevance to risk of breast cancer is unclear. The aim of this meta-analysis was to assess the effects of isoflavone-rich foods or supplements on a biomarker of breast cancer risk, women's mammographic density.
Electronic searches were performed on The Cochrane Library, Medline and EMBASE (to June 2009), and reference lists and trial investigators were consulted to identify further studies. Randomized controlled trials (RCTs) of isoflavone-rich foods or supplements versus placebo with a duration of at least 6 months were included in our analysis. Inclusion/exclusion, data extraction and validity assessment were carried out independently in duplicate, and meta-analysis used to pool study results. Subgrouping, sensitivity analysis, assessment of heterogeneity and funnel plots were used to interpret the results.
Eight RCTs (1287 women) compared isoflavones with placebo for between 6 months and 3 years. Meta-analysis suggested no overall effect of dietary isoflavones on breast density in all women combined [mean difference (MD) 0.69%, 95% confidence interval (CI) -0.78 to 2.17] or post-menopausal women (MD -1.10%, 95% CI -3.22 to 1.03). However, there was a modest increase in mammographic density in premenopausal women (MD 1.83%, 95% CI 0.25-3.40) without heterogeneity but this effect was lost in one of three sensitivity analyses.
Isoflavone intake does not alter breast density in post-menopausal women, but may cause a small increase in breast density in premenopausal women. Larger, long-term trials are required to determine if these small effects are clinically relevant.

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    • "mors significantly decreased when prepubertal rats were exposed to soy extracts or the isoflavone genistein ( Warri et al . , 2008 ) . Soy isoflavone is similar to the structure of endogenous estrogen , thus , it is a competitive inhibitor of endogenous estrogen and then protect against breast cancer ( Limer et al . , 2004 ; Magee et al . , 2004 ; Hooper et al . , 2010 ) . Soy isoflavones also have other protective effects , including antioxidant , anti - proliferative , anti - inflammatory and anti - angiogenic effect ( Heber , 2004 ) . A meta - analysis of 47 studies indicated that soy or soy isoflavone can significantly reduce the level of follicle - stimulating hormone and luteinizing hormone in p"
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    • "Epidemiological, clinical, and preclinical (animal) studies have provided ample evidence indicating that breast cancer development can be influenced by diet and lifestyle (Brennan et al. 2010, Patterson et al. 2010). High consumption of soy-rich foods containing genistein (GEN) is considered to partly underlie the lower breast cancer incidence in Asian women than in their western counterparts (Wu et al. 2008, Hooper et al. 2010). The antitumor effects of soy foods and bioactive GEN have been demonstrated in many rodent models of breast cancer (Jin & MacDonald 2002, Simmen et al. 2005, Su et al. 2007b, Verheus et al. 2007, Wu et al. 2008) to occur through multiple mechanisms. "
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    • "Similarly, a randomized control trial within the alpha-Tocopherol, beta-Carotene Cancer Prevention Study (22) suggested flavonoid-rich diets (flavonols, flavan-3-ols, kaempferol, quercetin , catechin, and epicatechin) may decrease pancreatic cancer risk in male smokers who did not consume supplemental alpha-tocopherol and=or beta-carotene. Also, results of the Multiethnic Cohort Study (23) revealed TABLE 4 Meta-analyses on the Effects of Flavonoids on Cancer Risk Tumor=Subtype Outcome Reference Prostate Protective effect of green tea for prostate cancer in one randomized control trial Boehm et al., 2009 (8) Intakes of genistein and daidzein were associated with lower risk of prostate cancer Hwang et al., 2009 (47) Protective effect for green tea but not black tea in Asian populations Zheng et al., 2011 (89) Breast Reduced cancer risk with soy isoflavones in Asian and postmenopausal women Dong and Qin, 2011 (6) Increased breast density in premenopausal women with soy isoflavones Hooper et al., 2010 (135) Small reduction in risk with soy intake Trock et al., 2006 (138) Reduced cancer risk with increased soy intake Wu et al., 2008 (139) Reduced cancer risk with green tea consumption Sun et al., 2006 (90) Trend for reduced risk with green tea consumption of ! 5 cups=d Seely et al., 2005 (91) Lung Reduced risk in some populations Tang et al., 2009 (155) Reduced 18% risk with an increased green tea (2 cups=d) consumption Tang et al., 2009 (92) Ovarian No association between coffee and tea consumption and cancer risk in EPIC study Braem et al., 2012 (97) Trend for a protective effect of green tea Nagle et al., 2010 (93) Protective role of green tea on ovarian and endometrial cancers Butler et al., 2011 (94) No association between tea consumption and risk of ovarian cancer Zhou et al., 2007 (98) No association between tea and coffee drinking and ovarian cancer Steevens et al., 2007 (99) Endometrial Reduced risk by 25% with 2 cups=d Tang et al., 2009 (103) Liver Protective effect of green tea for primary tumors Sing et al., 2011 (95) Gastric Protective effect of green tea (! 5 cups=d) Kang et al., 2010 (96) No association between green tea consumption and cancer risk Zhou et al., 2008 (100) No preventive effect of green tea Myung et al., 2009 (101) Colon No association with green and black tea consumption Sun et al., 2006 (102) Flavonoids and Cancer Prevention 213 the intake of total flavonols, in particular kaempferol, was inversely related to risk of pancreatic cancer (OR for kaempferol ¼ 0.78), although this study had a relative large 95% CI (0.58–1.05). Inverse relationships were also found among current smokers between risk of pancreatic cancer and intake of total flavonols (OR ¼ 0.41), quercetin (OR ¼ 0.55), kaempferol (OR ¼ 0.27), and myricetin (OR ¼ 0.55) (Table 3). "
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